Akihiro Aioi
Development Laboratory, SEPTEM-SOKEN Co., Ltd.,
Tomozumi Imamichi
Laboratory of Human Retrovirology and Immunoinformatics, Applied and Developmental Research Directorate

[Abstract]
Inflammaging has received considerable attention because aging is characterized by low-grade, chronic and asymptomatic inflammation, concomitant with increased blood levels of senescence-associated secretory phenotype (SASP) factors, including IL-1, IL-6, IL-8, IL-18 and tumor necrosis factor-α (TNF-α). On the other hand, IL-27 is not categorized as SASP factors though it is known that IL-27 has pleiotropic roles in inflammation. Here, we evaluated the interaction between TNF-α and IL-27 in the context of low-grade inflammation, using in HaCaT cells. TNF-α induced significant upregulation of IL-6 and IL-8α while the mRNA expression levels of IL-1RA, IL-10 and IL-18BP were unchanged. After confirming the functional expression of IL-27 receptor in HaCaT cells, we examined the effects of IL-27 alone on the cytokine expression. IL-27 alone significantly enhanced mRNA expression levels of IL-10 and IL-18BP, and also enhanced mRNA expression levels of IL-6. In the presence of 100ng/ml IL-27, the expression levels of anti-inflammatory cytokines, IL-1RA, IL-10 and IL-18BP, were significantly upregulated with the treatment of a physiological concentration (1ng/ml) TNF-α. Taken together, a high concentration of IL-27 exhibits anti-inflammatory effects in the presence of TNF-α when keratinocytes are the recipient of IL-27 signaling, suggesting the anti-inflammatory roles of IL-27 in inflammaging may be regulated by TNF-α concentration.